1. Technical Field of the Invention
The present invention relates to compositions wherein a high concentration of a material with dermal anchoring/skin mechanical properties, such as high (more than 30%) glycerin, acts to enhance the effect of active ingredients, such as the anti-microbial agent chlorhexidine gluconate (CHG).
2. Background of the Invention
A variety of creams, lotions, washes and foams have been developed as an adjunct to protective gloves to sanitize and protect the skin from both the transmission and the receipt of infectious agents. These products contain a variety of wetting agents, fatty acids, solvents, emollients and other agents which act to protect the skin in a variety of ways. However, concern has been raised about the effect of these additives on a variety of active ingredients such as germicides (Larson, E., et al., Effects of a Protective Coating Foam on Scrubbing and Gloving, AMERICAN J. OF INFECTION CONTROL 21 (6): 297 (1993)). For example, it is taught that chlorhexidine and its derivatives are inhibited by a variety of ingredients including anionic surfactants, soaps, gums, sodium alginate, magnesium aluminum silicate, magnesium trisilicate, bentonite, talc, kaolin, high pH, 3% lecithin/polysorbate 80 and polysorbate: 80 (Interaction between Cosmetic Ingredients and Preservatives, COSMETICS & TOILETRIES 110: 81-86 (1995)). To address this concern, investigators have performed studies on the effect of various additives on the efficacy of active ingredients.
Kihara, for example, teaches that the bactericidal activity of chlorhexidine digluconate and benzalkonium chloride (BAC) decreases in the presence of other ingredients such as serum, polysaccharides, non-ionic surfactants, powdered milk, dried bovine serum albumin, fish powder and other organic substances (U.S. Pat. No. 5,017,617). Kihara states that most emollients used in cosmetics are nonionic surfactants or higher alcohols, so it is likely that they decrease the bactericidal activity of chlorhexidine digluconate and benzalkonium chloride. Therefore, Kihara tested a variety of emollients, including diesters of dibasic acids, triesters of citric acid or phosphoric acid, and polyglycerol (2 to 15 monomers), for their effect on chlorhexidine digluconate. Surprisingly, Kihara found that these di- and tri-esters enhanced, rather than inhibited, bactericidal activity. Kihara employs low concentrations of emollient (0.1-1.0%) in 50-95% ethanol and teaches that higher concentrations of emollient are to be avoided as producing a sticky feel. The mechanism of enhancement is not provided by Kihara, but it is possible that the long carbon chain, polar emollient molecules act on the bacterial membranes themselves, thus assisting the bactericidal effect of chlorhexidine digluconate.
Similarly, in JP 63057502 assigned to Saraya, the inventors found that in alcohol disinfecting solutions containing chlorhexidine gluconate (CHG) and an emollient selected from the group of diisopropyl adipate, diisobutyl adipate, higher fatty acid polyoxethylene glycerol and polyglycerol, the emollient enhanced the effect of CHG. Again, it may be that the long chain, fatty acids alone or in combination with CHG act on the bacterial membranes to assist the bactericidal effect of CHG alone.
Loosemore tested the effect of polyvinyl alcohol and propylene glycol on the germicidal activity of 0.6% CHG in a teat dip application (U.S. Pat. No. 5,641,498). Loosemore reported that neither ingredient adversely affected the activity of CHG. Although Loosemore's compositions contained 4% glycerin (also known as glycerol or glycerine), he neglected to compare the effect of this particular agent on the activity of CHG.
Others, however, have studied the effect of glycerin on particular active ingredients. Mundschenk, for example, studied the effect of glycerin on the efficacy of hydrogen peroxide as an anti-microbial agent in a dental cream (U.S. Pat. No. 5,512,278). Mundschenk reported that 20% glycerin did not negate the effectiveness of 3% hydrogen peroxide in this particular application. Similarly, Turck showed that addition of up to 10% glycerin did not decrease the anti-microbial activity of the disinfectant N,N-dimethyldodecanamine on liquid cultures of Streptococcus agalactiae or Escherichia coli (Turck, P. A., et al. Mastitis: Effect of pH, Temperature and emollients on Disinfecting Action of N,N-dimethyldodecanamin, J. DAIRY SCI. 65(10): 1987 (1982)), and Hicks showed that up to 6% glycerin did not affect the efficacy of chlorhexidine digluconate in a teat dip application (Hicks W. G., et al., Evaluation of a Teat Dip of Chlorhexidine Digluconate (0.5%) with Glycerin (6%), J. DAIRY SCI. 64(11): 2266 (1981)).
Asaka teaches the use of 0.1-15% glycerin as an emollient used in combination with 25-80% lower alcohol, 0.01-4% cationic disinfectant such as CHG, and 1-40% amphoteric surfactant such as imidazolinium betaine (Australian Application No. AU-A-74370/94). Asaka notes that the emollients did not affect the disinfection by the cationic disinfectant, but states that concentrations higher than 15% may produce stickiness. Asaka's data shows that low levels of glycerin do not enhance the activity of CHG.
JP 61130210 assigned to San-Star showed that a paste containing CHG, 0.1-1% citric acid and 1-5% carrageenan improved the stability of CHG. A sample composition that also contained 30%. glycerin was provided.
To date no one has studied the effect of high levels of glycerin and similar compounds on the efficacy of active ingredients such as the anti-microbial chlorhexidine gluconate.